Aspirin and Statins in Chronic Hepatitis B: It's Complicated

Emily Willingham

November 19, 2020

For patients with chronic hepatitis B, the protective effects of aspirin against hepatocellular carcinoma (HCC) can vary with cirrhosis status and statin treatment, a pair of new studies finds.

One study showed that although aspirin is linked to a reduction in risk for HCC in these patients, comedication with statins could explain some of that effect. The other showed that cirrhosis dampens the risk-reduction benefit of aspirin.

Currently, there is a link between a reduction in HCC risk and aspirin or statins in patients with chronic hepatitis B, said investigator Won-Mook Choi, MD, PhD, from the University of Ulsan College of Medicine, in Seoul, Republic of Korea.

In one of their analyses, Choi and his colleagues teased out the contribution of each drug, and found that the decrease in HCC risk conferred by statins is similar whether or not patients also take aspirin.

"Only statins showed consistent and significant dose-dependent reductions in the risk of HCC, regardless of study design," said Choi, who presented the findings at The Liver Meeting 2020.

The second study, which looked at the association between aspirin and the risk for HCC in patients with and without cirrhosis, was presented by Heejoon Jang, MD, from the Seoul National University College of Medicine.

Aspirin was shown to be associated with a reduced risk for HCC, but cirrhosis "had a substantial effect on this association," erasing the benefit of aspirin, Jang reported.

Statins and Aspirin

Statins and aspirin are more likely to be prescribed together for patients with chronic hepatitis B but no cirrhosis, said Choi. For that reason, he and his colleagues analyzed data from the Korean National Health Insurance Service database from 2005 to 2015.

In their nested case–control analysis, 17,150 patients with HCC were matched for sex, age, and other factors to 817,675 patients without HCC. All participants had chronic hepatitis B without cirrhosis and had never received antiviral treatment.

The team also analyzed the incidence of HCC in two historic cohorts of patients with chronic hepatitis B but no cirrhosis, one consisting of 673,107 people who took aspirin and the other with 588,045 who took statins.

The nested case–control analysis showed an 11% risk reduction with aspirin use (adjusted odds ratio [OR], 0.89; 95% CI, 0.85 - 0.94) and a 61% risk reduction with statin use (adjusted OR, 0.39; 95% CI, 0.36 - 0.40). There was a dose-response effect with statins, but not with aspirin.

The historic cohort analysis showed a 33% reduction in the risk for HCC with aspirin (adjusted hazard ratio [HR], 0.67; 95% CI, 0.63 - 0.72) and a 67% reduction with statins (adjusted HR, 0.33; 95% CI, 0.30 - 0.37). However, stratified analyses by drug showed a statin benefit with or without aspirin (P < .001 for both), but no aspirin benefit without statins.

Cirrhosis and Aspirin

To assess the interaction between cirrhosis and aspirin, Jang and his colleagues identified 329,635 patients with chronic hepatitis B in the Korean National Health Insurance Service database.

A total of 20,200 had taken aspirin for at least 90 consecutive days, and the rest had never received antiplatelet therapy. Treated and untreated patients were matched for several factors, and HCC incidence was assessed after a median follow-up of 6.7 years.

Among the 2697 patients who developed HCC during follow-up, the cumulative incidence of HCC was significantly lower for those who took aspirin than for those who did not (P < .001). There was a 15% reduction in the risk for HCC in the aspirin group (adjusted HR, 0.85; 95% CI, 0.78 - 0.92).

However, in patients with cirrhosis, the benefit of aspirin disappeared. Patients without cirrhosis still had a 13% reduction in risk for HCC (adjusted HR, 0.87: 95% CI, 0.79 - 0.95). This group also had a slightly elevated risk for major bleeding (adjusted HR, 1.1; 95% CI, 1.03 - 1.28).

The findings from these two studies add to a growing body of literature that shows the promise of statins and aspirin, which are both readily available and relatively safe, said Amit Singal, MD, from the UT Southwestern Medical Center in Dallas, who was not involved with either study.

"The studies are relatively simple but really do tackle an area of immense need in the field," he said. Short of having higher-quality data, however, statins and aspirin aren't quite ready to become bespoke chemotherapies in the clinic, he added, although the results show promise for future randomized trials.

The subgroup analyses that looked at cirrhosis and the interplay of aspirin and statins can help with the planning of such trials, which "is really important for trial design, Singal noted.

He also pointed to studies that, unlike these results, have found a benefit of aspirin in patients with cirrhosis, underscoring the need for randomized trials. However, "each study does provide a data point that can help to inform those trials," he said.

Choi and Jang have disclosed no relevant financial relationships. Singal is a consultant for Genentech, Bayer, Eisai, Exelixis, Bristol-Myers Squibb, Roche, Glycotest, FujiFilm, GRAIL, and Exact Sciences, primarily in relation to HCC treatment and screening, not chemoprevention.

The Liver Meeting Digital Experience 2020: American Association for the Study of Liver Diseases (AASLD): Abstracts 137 and 159. Presented November 16, 2020.

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